The influence of various chemical effectors on V(D)J recombination in early lymphoid cells has been studied. The test system uses recombinational target sequences on extrachromosomal plasmids which provide a good assay of overall V(D)J recombinase activity in the cells. Several effectors whose common focus is an ultimate increase in the cellular level of cyclic AMP(cAMP) produce large increases in V(D)J recombination (3 to 8-fold). These compounds--caffeine, theophylline, forskolin, and 8-bromo-cAMP--act in different ways but produce similar results. Because the major effect of cAMP in mammalian cells is the stimulation of protein kinase A, effectors of other protein kinase were also studied. Phorbol myristate acetate, a stimulator of protein kinase C, reduces recombination about 4-fold, and a similar effect is seen with the calcium ionophore A23187, a stimulator of both protein kinase C and the calcium/calmodulin dependent protein kinase. We conclude that V(D)J recombination activity is strongly influenced by chemical signaling pathways.